4-Methylmorpholine → 5-(3-(4-Fluoro-2-methoxyphenoxy)quinoxaline-2-carboxamido)picolinic acid

Participants

Reaction Conditions

Reaction Steps

A solution of the 5-aminopicolinic acid methyl ester (15.2 mg, 0.1 mmol), 3-(4-fluoro-2-methoxy-phenoxy)quinoxaline-2-carboxylic acid (34.57 mg, 0.11 mmol), N-methylmorpholine (21.99 μL, 0.2 mmol) and HATU (45.6 mg, 0.12 mmol) in DMF (0.4 mL) was stirred at 40° C. for 16 hours. 3M aqueous NaOH solution (0.50 mmol, 166.7 μL) and methanol (0.2 mL) was added and the reaction mixture was stirred at 40° C. for 1 hour. The mixture was diluted with MeOH, filtered and purification by reverse phase HPLC using a gradient of 1-99% ACN in water and HCl as a modifier to yield 5-(3-(4-fluoro-2-methoxyphenoxy)quinoxaline-2-carboxamido)picolinic acid (32) (10.75 mg, 23%). ESI-MS m/z calc. 434.10, found 435.3 (M+1)+; Retention time: 1.33 minutes (3 minutes run). 1H NMR (400 MHz, DMSO) δ 13.12 (s br, 1H), 11.52 (s, 1H), 9.06 (d, J=2.3 Hz, 1H), 8.45 (dd, J=8.6, 2.5 Hz, 1H), 8.20 (d, J=7.8 Hz, 1H), 8.14 (d, J=8.6 Hz, 1H), 7.82 (ddd, J=24.3, 15.6, 6.7 Hz, 3H), 7.36 (dd, J=8.8, 5.8 Hz, 1H), 7.16 (dd, J=10.6, 2.8 Hz, 1H), 6.88 (ddd, J=8.5, 2.8 Hz, 1H), 3.70 (s, 3H) ppm.

Provenance & Evidence